Tags

Type your tag names separated by a space and hit enter

Ovariectomy-Induced Mitochondrial Oxidative Stress, Apoptosis, and Calcium Ion Influx Through TRPA1, TRPM2, and TRPV1 Are Prevented by 17β-Estradiol, Tamoxifen, and Raloxifene in the Hippocampus and Dorsal Root Ganglion of Rats.
Mol Neurobiol. 2017 Dec; 54(10):7620-7638.MN

Abstract

Relative 17β-estradiol (E2) deprivation and excessive production of mitochondrial oxygen free radicals (OFRs) with a high amount of Ca[2+] influx TRPA1, TRPM2, and TRPV1 activity is one of the main causes of neurodegenerative disease in postmenopausal women. In addition to the roles of tamoxifen (TMX) and raloxifene (RLX) in cancer and bone loss treatments, regulator roles in Ca[2+] influx and mitochondrial oxidative stress in neurons have not been reported. The aim of this study was to evaluate whether TMX and RLX interactions with TRPA1, TRPM2, and TRPV1 in primary hippocampal (HPC) and dorsal root ganglion (DRG) neuron cultures of ovariectomized (OVX) rats. Forty female rats were divided into five groups: a control group, an OVX group, an OVX+E2 group, an OVX+TMX group, and an OVX+RLX group. The OVX+E2, OVX+TMX, and OVX+RLX groups received E2, TMX, and RLX, respectively, for 14 days after the ovariectomy. E2, ovariectomy-induced TRPA1, TRPM2, and TRPV1 current densities, as well as accumulation of cytosolic free Ca[2+] in the neurons, were returned to the control levels by E2, TMX, and RLX treatments. In addition, E2, TMX, and RLX via modulation of TRPM2 and TRPV1 activity reduced ovariectomy-induced mitochondrial membrane depolarization, apoptosis, and cytosolic OFR production. TRPM2, TRPV1, PARP, and caspase-3 and caspase-9 expressions were also decreased in the neurons by the E2, TMX, and RLX treatments. In conclusion, we first reported the molecular effects of E2, TMX, and RLX on TRPA1, TRPM2, and TRPV1 channel activation in the OVX rats. In addition, we observed neuroprotective effects of E2, RLX, and TMX on oxidative and apoptotic injuries of the hippocampus and peripheral pain sensory neurons (DRGs) in the OVX rats. Graphical Abstract Possible molecular pathways of involvement of DEX in cerebral ischemia-induced apoptosis, oxidative stress, and calcium accumulation through TRPA1, TRPM2 and TRPV1 in the hippocampus and DRG neurons of rats. The N domain of the TRPM2 contains ADP-ribose (ADPR) pyrophosphate enzyme, which is separately activated by ADPR and oxidative stress, although the channel is reversibly inhibited by N-(p-amylcinnamoyl) anthranilic acid (ACA). The TRPV1 is also activated by mitochondrial oxidative stress and capsaicin, and it is blocked by capsazepine (CPZ). TRPA1 is also activated by oxidative stress it is inhibited by AP18. Increased cytosolic Ca[2+] concentration through TRPA1, TRPM2 and TRPV1 in ovariectomized (OVX) rats may lead to neuronal toxicity, reactive oxygen species (ROS) processes, and eventual cell death. 17β-Estradiol (E2), tamoxifen (TMX), and raloxifene (RLX) reduced oxidative stress, apoptosis (including caspase-3 and caspase-9), mitochondrial membrane depolarization, and Ca[2+] influx through the inhibition of TRPA1, TRPM2 and TRPV1 activation.

Authors+Show Affiliations

Department of Biophysics, Institute of Health Science, Suleyman Demirel University, Isparta, Turkey.Department of Biophysics, Institute of Health Science, Suleyman Demirel University, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr. Neuroscience Research Center, University of Suleyman Demirel, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr. Nörolojik Bilimler Uygulama ve Araştırma Merkezi Müdürü, Süleyman Demirel Üniversitesi, TR 32260, Isparta, Turkey. mustafanaziroglu@sdu.edu.tr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27832523

Citation

Yazğan, Yener, and Mustafa Nazıroğlu. "Ovariectomy-Induced Mitochondrial Oxidative Stress, Apoptosis, and Calcium Ion Influx Through TRPA1, TRPM2, and TRPV1 Are Prevented By 17β-Estradiol, Tamoxifen, and Raloxifene in the Hippocampus and Dorsal Root Ganglion of Rats." Molecular Neurobiology, vol. 54, no. 10, 2017, pp. 7620-7638.
Yazğan Y, Nazıroğlu M. Ovariectomy-Induced Mitochondrial Oxidative Stress, Apoptosis, and Calcium Ion Influx Through TRPA1, TRPM2, and TRPV1 Are Prevented by 17β-Estradiol, Tamoxifen, and Raloxifene in the Hippocampus and Dorsal Root Ganglion of Rats. Mol Neurobiol. 2017;54(10):7620-7638.
Yazğan, Y., & Nazıroğlu, M. (2017). Ovariectomy-Induced Mitochondrial Oxidative Stress, Apoptosis, and Calcium Ion Influx Through TRPA1, TRPM2, and TRPV1 Are Prevented by 17β-Estradiol, Tamoxifen, and Raloxifene in the Hippocampus and Dorsal Root Ganglion of Rats. Molecular Neurobiology, 54(10), 7620-7638. https://doi.org/10.1007/s12035-016-0232-5
Yazğan Y, Nazıroğlu M. Ovariectomy-Induced Mitochondrial Oxidative Stress, Apoptosis, and Calcium Ion Influx Through TRPA1, TRPM2, and TRPV1 Are Prevented By 17β-Estradiol, Tamoxifen, and Raloxifene in the Hippocampus and Dorsal Root Ganglion of Rats. Mol Neurobiol. 2017;54(10):7620-7638. PubMed PMID: 27832523.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ovariectomy-Induced Mitochondrial Oxidative Stress, Apoptosis, and Calcium Ion Influx Through TRPA1, TRPM2, and TRPV1 Are Prevented by 17β-Estradiol, Tamoxifen, and Raloxifene in the Hippocampus and Dorsal Root Ganglion of Rats. AU - Yazğan,Yener, AU - Nazıroğlu,Mustafa, Y1 - 2016/11/10/ PY - 2016/08/19/received PY - 2016/10/16/accepted PY - 2016/11/11/pubmed PY - 2018/7/3/medline PY - 2016/11/11/entrez KW - Hippocampus KW - Ovariectomy KW - Raloxifene KW - TRPM2 KW - TRPV1 KW - Tamoxifen SP - 7620 EP - 7638 JF - Molecular neurobiology JO - Mol Neurobiol VL - 54 IS - 10 N2 - Relative 17β-estradiol (E2) deprivation and excessive production of mitochondrial oxygen free radicals (OFRs) with a high amount of Ca[2+] influx TRPA1, TRPM2, and TRPV1 activity is one of the main causes of neurodegenerative disease in postmenopausal women. In addition to the roles of tamoxifen (TMX) and raloxifene (RLX) in cancer and bone loss treatments, regulator roles in Ca[2+] influx and mitochondrial oxidative stress in neurons have not been reported. The aim of this study was to evaluate whether TMX and RLX interactions with TRPA1, TRPM2, and TRPV1 in primary hippocampal (HPC) and dorsal root ganglion (DRG) neuron cultures of ovariectomized (OVX) rats. Forty female rats were divided into five groups: a control group, an OVX group, an OVX+E2 group, an OVX+TMX group, and an OVX+RLX group. The OVX+E2, OVX+TMX, and OVX+RLX groups received E2, TMX, and RLX, respectively, for 14 days after the ovariectomy. E2, ovariectomy-induced TRPA1, TRPM2, and TRPV1 current densities, as well as accumulation of cytosolic free Ca[2+] in the neurons, were returned to the control levels by E2, TMX, and RLX treatments. In addition, E2, TMX, and RLX via modulation of TRPM2 and TRPV1 activity reduced ovariectomy-induced mitochondrial membrane depolarization, apoptosis, and cytosolic OFR production. TRPM2, TRPV1, PARP, and caspase-3 and caspase-9 expressions were also decreased in the neurons by the E2, TMX, and RLX treatments. In conclusion, we first reported the molecular effects of E2, TMX, and RLX on TRPA1, TRPM2, and TRPV1 channel activation in the OVX rats. In addition, we observed neuroprotective effects of E2, RLX, and TMX on oxidative and apoptotic injuries of the hippocampus and peripheral pain sensory neurons (DRGs) in the OVX rats. Graphical Abstract Possible molecular pathways of involvement of DEX in cerebral ischemia-induced apoptosis, oxidative stress, and calcium accumulation through TRPA1, TRPM2 and TRPV1 in the hippocampus and DRG neurons of rats. The N domain of the TRPM2 contains ADP-ribose (ADPR) pyrophosphate enzyme, which is separately activated by ADPR and oxidative stress, although the channel is reversibly inhibited by N-(p-amylcinnamoyl) anthranilic acid (ACA). The TRPV1 is also activated by mitochondrial oxidative stress and capsaicin, and it is blocked by capsazepine (CPZ). TRPA1 is also activated by oxidative stress it is inhibited by AP18. Increased cytosolic Ca[2+] concentration through TRPA1, TRPM2 and TRPV1 in ovariectomized (OVX) rats may lead to neuronal toxicity, reactive oxygen species (ROS) processes, and eventual cell death. 17β-Estradiol (E2), tamoxifen (TMX), and raloxifene (RLX) reduced oxidative stress, apoptosis (including caspase-3 and caspase-9), mitochondrial membrane depolarization, and Ca[2+] influx through the inhibition of TRPA1, TRPM2 and TRPV1 activation. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/27832523/Ovariectomy_Induced_Mitochondrial_Oxidative_Stress_Apoptosis_and_Calcium_Ion_Influx_Through_TRPA1_TRPM2_and_TRPV1_Are_Prevented_by_17β_Estradiol_Tamoxifen_and_Raloxifene_in_the_Hippocampus_and_Dorsal_Root_Ganglion_of_Rats_ DB - PRIME DP - Unbound Medicine ER -